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The Prospect of Pharmacogenetics in Pediatrics

By | Opioids, Other, Pharmacogenetic Testing, Provider | No Comments

Pharmacogenetics of Opioids as a Potential Alternative in Pediatric Pain Management

 
Opioid and codeine treatment in pain management for children has been a primary concern in clinical settings, specifically for surgical pain management. The concerns are the adverse reactions caused by the opioids, such as respiratory depression. Current Opinion in Anesthesiology, “Codeine and Opioid Metabolism: Implications and Alternatives for Pediatric Pain Management” (2017), reviews how important clinical factors and genetic polymorphisms affect the metabolism of opioids after surgical operations.

 

Adverse Side Effects of Codeine

 
Codeine’s efficacy has been questioned in the pain management of children. Current Opinion in Anesthesiology identifies the adverse reactions of it. The prominent ones are respiratory depression, anoxic brain injuries, and even death occurring in children. With reported doses of codeine, significant respiratory depression was found in newborns in a report by Canadian Pharmacists Journal “Pain Management in Children: A Transition from Codeine to Morphine for Moderate to Severe Pain in Children” (2012).

 
Opioids in Pain Management

 
Opioids are the cornerstone of pain and chronic pain management. “Successful pain management provides adequate analgesia without excessive adverse reactions affirms Clinical Biochemistry “Pharmacogenetics of Chronic Pain Management” (2014). Drug metabolism and responses are influenced by numerous factors, including pharmacogenetics. Genetic variations contribute to the distinct inter individual responses to pain medications.

 
Involvement of CYP2D6 in Codeine

 
Those with two nonfunctional alleles of CYP2D6 are considered poor metabolizers. Extensive metabolizers have one or two effective CYP2D6 alleles and those with duplicated CYP2D6 alleles are ultra rapid metabolizers. Canadian Pharmacists Journal indicates the functions of CYP2D6 are similar in both children and adults.

 
The review also acknowledges the safety concerns of CYP2D6 ultra rapid metabolizers from several studies. One study demonstrated how a breastfed newborn infant died after his mother consumed Tylenol #3 for postpartum pain. Toxicology testing found the mother had abnormally high concentration levels of morphine in her breast milk. Genotype testing found the mother was an ultra rapid metabolizer of codeine. The study concluded since the mother was an ultra rapid metabolizer, higher than normal morphine levels crossed into the breast milk and resulted in the infant dying from morphine intoxication.

 
Another study found a two-year-old child who also died of morphine intoxication. The child was prescribed codeine in recommended dosages after having his tonsils removed. Genotype testing revealed the child was an ultra rapid metabolizer of codeine. However, there were also other contributing factors; the child had bronchopneumonia and sleep apnea. The study concluded these factors “may have increased his risk of hypoxemia, leading to alterations in opioid receptors and increased sensitivity to morphine.”

 
Canadian Pharmacists Journal concludes these studies show ultra rapid metabolizers of codeine are correlated with a higher risk of morphine intoxication among children.

 

Alternatives to Prevent Adverse Drug Reactions

 
Canadian Pharmacists Journal argues morphine as a safer alternative compared to codeine. They argue morphine has “demonstrated efficacy and relative safety when used appropriately in pain management in both adults and children.” A study they analyzed found morphine treatment more effective than a placebo for children in postoperative pain.

 
Current Opinion in Anesthesiology also outlines the possible alternatives to prevent the risks of opioids, such as pharmacogenetics. They indicate personalized opioid therapy for pain management is “distant from reality”, but current CYP2D6 pharmacogenetic research on codeine is hopeful. The review summarizes, “pharmacogenetics has the potential to guide anesthesia providers on perioperative opioid selection and dosing to maximize efficacy and safety.”

Pharmacogenetics Emerging as a Method to Guide Medication Therapy

By | Gene Panel, Opioids, Other, Pharmacogenetic Testing, Provider | No Comments

According to a recent article published in American Family Physician “Pharmacogenetics: Using Genetic Data to Guide Drug Therapy (2015), pharmacogenetics is being more widely used by family physicians and the number of patients who are interested in acquiring genetic information is growing.

 

The Components of Pharmacogenetics Testing

 
Pharmacogenetics involves genetic variations that code for drug metabolizing enzymes. It also involves how a medication breaks down in the body and how the body responds to the medication. The most common forms of genetic variations are single nucleotide polymorphisms.

 
The differences in single nucleotide polymorphisms or other polymorphisms result in diverse types of genes or alleles, the American Family Physician explains. Individuals inherit these alleles that “govern expression of the gene and the cor¬responding enzyme or protein.” As a result, these genetic differences influence how the drug reacts in the body and how the body metabolizes the drug.

 

Genetic Variability Can Alter the Effects of Drugs

 
Studies have demonstrated there is a connection between genetic variations and changes in drug levels and effects.

 
CYP2D6 and Opioids

 
The enzyme activity of CYP2D6 is volatile because of single nucleotide polymorphisms and other variations of CYP2D6. American Family Physician indicates codeine metabolism occurs in 90% of patients and results in normal morphine formation. However, 1% to 2% of people are ultra rapid metabolizers of codeine signifying they have an increased risk of morphine toxicity.

 
American Family Physician analyzed a study involving the death of a breastfed infant and a mother who was an ultra rapid metabolizer of codeine. The study demonstrated the infant died of morphine intoxication. There was opioid toxicity in the breast milk, which passed onto the infant.

 
They recommend pharmacogenetic testing for patients who are possible poor or ultra rapid metabolizers of opioids.

 

CYP2C19 and Clopidrogrel

 
Clopidogrel is primarily metabolized in the enzyme CYP2C19. CYP2C19 is highly polymorphic and 80% of individuals metabolize clopidogrel normally. However, 18% to 45% of people have intermediate enzyme activity and 2% to 15% have poor enzyme activity.

 
American Family Physician presents meta-analyses of CYP2C19 poor metabolizers. Poor CYP2C19 metabolizers taking clopidogrel treatment and undergoing percutaneous coronary intervention have a higher risk of cardiovascular death, myocardial infraction, stroke, and stent thrombosis.

 
These results lead to the recommendation that clinicians should consider alternative treatments, such as pharmacogenetic testing of CYP2C19 to guide antiplatelet therapy.

 

The Benefits of Pharmacogenetics

 
American Family Physician examined the clinical implications of pharmacogenetic testing and the various resources available and developing to support the usage of pharmacogenetics in clinical settings. They conclude “pharmacogenetic testing can be a practical tool to optimize drug therapy and avoid medication adverse effects.”

Statin Side Effects: From Muscle Soreness to Rhabdomyolysis

By | Adverse Drug Reactions, Statins | No Comments

Statins are drugs used to lower cholesterol. They are effective agents for treating high cholesterol, enabling your liver to remove cholesterol from your blood, which lowers your total cholesterol. Lowering LDL (low-density lipoprotein, or “bad”) cholesterol results in substantial reductions in cardiac events. Statins also help prevent other cardiovascular diseases, such as chest pain, heart attacks, strokes, and certain blood vessel problems (Pharmacy Times “Statins Provide Heart Benefits Besides Cholesterol Lowering” June 1 2017).

 

Statins approved for use in the United States include the following agents: atorvastatin (Lipitor), fluvastatin (Lescol), lovastatin (Mevacor), pravastatin (Pravachol), rosuvastatin (Crestor), simvastatin (Zocor), and pitavastatin (Livalo).

 
One of the most common unwanted symptoms from taking statins is muscle pain, muscle soreness, muscle fatigue, and muscle weakness. People who take statins shouldn’t drink large quantities of grapefruit juice, as this is associated with the muscle pain side effects. Statins may affect specific enzymes present in muscle cells that are responsible for muscle growth. The muscle pain is located in skeletal muscle, and the side effects range from slight myalgia to severe rhabdomyolysis.

 

Rhabdomyolysis: Rapid Breakdown of Skeletal Muscle

Rhabdomyolysis is a serious condition in which the destruction of striated muscle tissue, or skeletal muscle, releases muscle enzymes such as myoglobin and electrolytes from inside the muscle cells. If you have too much myoglobin in your bloodstream it can cause kidney damage. If treated early, rhabdomyolysis may be stopped.   This condition is treated with fluids given in an IV drip. Some people may require dialysis or hemofiltration (therapy filtering bad waste and products from blood) to address the more severe cases.

 
Early symptoms of rhabdomyolysis may be vague as they are not specific and may mimic other conditions. The symptoms of rhabdomyolysis include:

 

  • Muscle weakness
  • Fatigue
  • Low urine output
  • Bruising/soreness
  • Dark or tea-colored urine
  • Infrequent urination
  • Fever
  • Malaise (discomfort)
  • Nausea/vomiting
  • Confusion
  • Agitation

 
Although only a minimal number of people get rhabdomyolysis, many people take these medications and it is important to be aware of the risks.

 

Importance of Determining Muscle and Kidney Health

 
There are several tests to check muscle and kidney health. Creatine kinase levels should be tested, as it is an enzyme found in the skeletal muscles, the brain, and the heart. Myoglobin levels in the blood and urine should also be tested, as myoglobin is a protein that is a byproduct of muscle breakdown. Potassium is an important mineral that may leak from injured muscles and should be tested as well. Lastly, creatine in blood and urine should be tested, as creatine is a breakdown product created by muscle that is normally removed from the body by the kidneys.

 
Rhabdomyolysis can be successfully treated without long-term damage to the kidneys if it is treated early. Fluid recovery is essential and is the first and most important treatment.

 

Statin Muscle Side Effects and Pharmacogenetics

 
Although few patients experience muscle pain and the associated serious side effects, it has been suggested that the basis for this reaction is genetic. Once the human genome was sequenced and completed, the field of pharmacogenetics could advance its knowledge base. Pharmacogenetics is an important medical field that studies the genes that are responsible for drug metabolism and related events. Advances in the wider field of pharmacogenomics showed that in a genome wide study, muscle myopathy was associated with single nucleotide polymorphisms (SNPs) in the gene SLCO1B1. Those authors identified common genetic variants in SLCO1B1 that are strongly associated with statin-induced myopathy.

 

Know Your Risks with the Rxight® Pharmacogenetic Test

 
Genotyping using the Rxight® pharmacogenetics test from MD Labs may help patients receive the benefits of statin therapy without the muscle-associated side effects. Pharmacogenetics testing with the Rxight® platform from MD Labs is an advanced, state-of-the-art method to test many gene variations in your individual genome that may be responsible for adverse effects with statins and over 200 other drugs on the market. This precision medicine approach to personalized care is now available by prescription.

 
Ask your physician to prescribe the Rxight® pharmacogenetics test from MD Labs. You and your physician may use these results over the lifetime of your care, as many genes are tested for variations that are responsible for adverse side effects not only in statins, but also in the majority of drugs on the market.

 
These results inform your physician about what drugs you may safely take, and what drugs are not recommended for you, in addition to giving dosing schedules that might be different from label instructions. Participating in this precision medicine advance may lead to lessened side effects over the course of your lifetime pharmaceutical treatments.

 

 

The Pharmacogenetics of Antiplatelet Agents: Meta-Analyses of Aspirin and Clopidogrel Loss-of-Function Alleles

By | Gene Panel, Other, Pharmacogenetic Testing | No Comments

 
Antiplatelet agents combined with aspirin have been shown to play a significant role in mitigating the effects of coronary disease, and ample research has found that distinct genetics determine patients’ response to clinically significant antiplatelet agents.

 

Platelets play a decisive role during the formation of an initial hemostatic plug through their intricate response to injury. When inappropriately activated, platelets contribute to pathological thrombus formation. Arterial thrombus formation can then lead to tissue ischemia causing potentially fatal coronary and cerebrovascular events.

 

Interindividual Genetic Variation Impacts Aspirin Antiplatelet Efficacy

 

Aspirin is regarded as “the cornerstone for secondary cardiovascular prevention,” the efficacy of it, which has long been established, as noted in Current Pharmaceutical Design, “Pharmacogenetics of the Antiplatelet Effect of Aspirin” (2012).

 

The researchers avert that there is considerable interindividual variation in response to aspirin, thus reducing its efficacy in treating heart disease in some patients.

 

P1A2 and P2Y1 Association with Decreased Aspirin Antiplatelet Efficacy

 

Specifically, the review conducted by Current Pharmaceutical Design examined polymorphisms of genes that contributed highly to antiplatelet responses. These were P1A2 from glycoprotein GP IIb/IIIa, and the P2Y1 polymorphism from AD receptor (ADP) genes.

 

P1A2 was characterized as having an association with coronary thrombus formation. One study showed P1A2 allele was related with a shorter baseline bleeding time in comparison to a wild type allele. After measuring bleeding after aspirin ingestion, there was a reduced antiplatelet effect.

 

Another study supported this finding by discovering an enhanced thrombin formation in P1A2 carriers compared to P1A1/A1 homozygotes before and after aspirin ingestion. The review concluded that P1/A2 polymorphism is a prothrombotic platelet phenotype responding inadequately to aspirin.

 

Polymorphism P2Y1 was utilized in an arachidonic acid-induced optical platelet aggregometry to assess its antiplatelet effect of aspirin. The results showed that the T allele of the C893T P2Y1 polymorphism was substantially linked with a decreased antiplatelet effect of aspirin.

 

CYP2C19 Mediates Clopidogrel Non-Response

 

Evidence for association of CYP2C19 with clopidogrel response was investigated in the Journal of Human Genetics “Pharmacogenomics of Anti-Platelet Therapy: How Much Evidence is Enough for Clinical Implementation?” (June 2013).

 

The study established CYP2C19 as a genetic factor contributing to the creation of the active metabolite of clopidogrel. A corresponding analysis detailing the associations of CYP2C19 alleles and increasing residual on-treatment platelet reactivity corroborated this finding. The study concluded that patients with even one reduced function of CYP2C19 and taking clopidogrel as treatment for percutaneous coronary intervention may be “associated with increased risk of major adverse cardiovascular events as a consequence of aspirin antiplatelet inefficacy.”

 

The International Journal of Environmental Research and Public Health “Pharmacokinetic and Pharmacodynamics Responses to Clopidogrel” (February 2017) also reviewed the connection between CYP2C19 and clopidogrel. The review was based on the authors’ argument that genetic polymorphisms impact the absorbtion and metabolism of clopidogrel and that the P2Y12 receptor may interfere with its antiplatelet activity.

 

In one meta-analysis, it was found there was a critical relation between CYPC219 loss-of-function in diverse patients with frequent cardiovascular events. In another meta-analysis, CYPC219 was identified as having a having a crucial part in reducing the active metabolite of clopidogrel.

 

CYP3A4/5 Mediates Clopidogrel Non-Response

 

In addition to analyzing clopidogrel, the review also analyzed CYP3A4/5. The authors found that the CYP3A5*3 allele has an influence on clopidogrel metabolism because of its possible dependence on CYP2C19 and CYP3A4 inhibitors. In the study, the patients with a CYP3A5*3/3 genotype displayed enhanced platelet reactivity compared to those with a CYP3A5*1 allele in CYP2C19 poor metabolizers. An additional study reported CYP3A5*3 on clopidogrel response is prominently in patients with the CYP2C19 loss-of-function.

 

 

Benefits of Individualizing Antiplatelet Therapy with Pharmacogenetic Testing

 

Research has been conclusive in identifying potential antiplatelet pharmacogenetic applications pointing to effective individualized treatments, according to the studies.

 
The review by the International Journal of Environmental Research and Public Health asserted there is an “inter-individual variability” in clopidogrel’s antiplatelet effects. They concluded inadequate platelet responsiveness to clopidogrel has a role in accumulating the risk of cardiovascular events, and therefore increasing drug dosage or switching to alternative drug medications may be more beneficial for patients.

 
Similarly, the review published in Current Pharmaceutical Design concludes by recommending utilization of antiplatelet pharmacogenetics in clinical practice. “The promise of pharmacogenetics lies in the prospect of improving treatment efficacy and safety.”

 

 

 

Overview of Alprazolam (Xanax) Uses and Side Effects

By | Adverse Drug Reactions, Antianxiety Medications, Other | No Comments

Alprazolam, commonly referred to by its brand name Xanax, is the one of the most common benzodiazepine used. Benzodiazepines like alprazolam are anxiolytics (antianxiety drugs) used in the treatment of a number of diseases including panic disorder, generalized anxiety disorder and social anxiety disorders. Occasionally the drug is used for nausea and vomiting symptoms associated with chemotherapy. (PubMed Health “Alprazolam” May 2017).

 

Alprazolam Mechanism of Action

Alprazolam, like all benzodiazepines, binds nonspecifically to benzodiazepine receptors at the BDZ site. This bind tightens the connection of GABA with the receptor and results in increasing hyperpolarization of neurons. This mechanism is the base for the drug’s antianxiety effects.

 

Alprazolam Side Effects

 
Alprazolam has a significant effect on a major neurotransmitter which results into psychiatric and nervous system side effects. According to the FDA label on Xanax, the most common adverse effects include (occur in more than 1% of patients):

 

  • Irritability
  • Anxiety
  •  Depression
  •  Confusion
  •  Derealization or alteration of perception
  •  Dream abnormalities
  •  Fear
  •  Disinhibition
  •  Drowsiness (77% of patients)
  • Impaired coordination (40% of patients)
  •  Memory impairment
  • Lightheadedness
  • Insomnia
  • Headache
  •  Cognitive disorder
  •  Dysarthria
  •  Ataxia
  •  Balance disorders
  •  Nasal congestion
  •  Hyperventilation
  •  Upper respiratory tract infections
  • Fatigue/tiredness (49%)
  •  Weakness
  •  Edema (swelling)
  •  Decreased libido (14%) and increased libido
  •  Micturition difficulties (inability to urinate etc)
  •  Menstrual disorders (in females)
  •  Sexual dysfunction
  •  Sweating
  •  Rash
  •  Allergies
  •  Tachycardia (increased heart rate)
  •  Chest pain
  •  Palpitations
  •  Hypotension
  •  Increased appetite (33%)/ decreased appetite (28%)
  •  Weight gain (27%)/ loss (23%)

The Xanax label from the FDA reports Alprazolam has rare side effects, which are anger, self-harm and irregular menstruation. These occur in less than 1% of patients

 
Risk of Suicide

 
Research has shown that the use of benzodiazepines can influence suicide risk.  A literature review evaluated studies that involved the relationship between benzodiazepines and concluded there was a significant relationship between increased suicide risk and benzodiazepines (The Primary Companion for CNS Disorders “Prescribed Benzodiazepines and Suicide Risk” March 2017). The results were consistent in different populations and methods used.  The review also found that possible suicidal warnings may include “increases in impulsivity or aggression, rebound or withdrawal symptoms, and toxicity in overdose.”

 
Alprazolam and Pharmacogenetic Testing

 
Some patients do not develop any side effects when taking Alprazolam and some do.  This interpatient variability may be due to differences in patients’ genetics. Polymorphisms in the genes that code for enzymes and receptors that interact with Alprazolam have been shown to account for a significant proportion of this inter patient variability.

 
Alprazolam is metabolized by the cytochrome P450 superfamily of enzymes, namely isoenzymes CYP3A4 and CYP2C9. Polymorphisms in these enzymes have been shown to alter the blood plasma concentrations of the drugs they metabolize. Alleles may alter the probability of individual developing side effects when taking Alprazolam.

 

Understand Your Genetic Risks for Side Effects with the Rxight Test

Identifying these polymorphisms can aid in clinical decision-making. Knowing a patient has a given polymorphism can result in a clinician altering the starting dose of a medication like Alprazolam, potentially reducing their probability of developing side effects.

 
MD Labs provides a genetic testing service, Rxight®.  Accurate, reliable, and easy to understand, Rxight® sequences 18 genes to establish how a patient is likely to respond to hundreds of clinically relevant medications (including Alprazolam).

 
As a key component of precision medicine, Rxight® allows your healthcare provider and pharmacist to see if Alprazolam is right for you and create the best possible treatment for you.  With a simple cheek swab done at your pharmacy, Rxight® will provide you with a DNA Blueprint that minimizes drug’s side effects and proper course for present and future treatments.

 
Contact us for more information about how Rxight® can benefit you through phone at 1-(888) 888-1932 or email at support@Rxight.com.

The Possible Connection Between Antianxiety Drug Lorazepam (Ativan) Use and Suicide

By | Adverse Drug Reactions, Antianxiety Medications | No Comments

Lorezapam, also known as the brand name Ativan, is a common antianxiety drug prescribed by psychiatrists. According to Pharmacy Times, it is the 48th most used drug in the United States (Pharmacy Times “Top 200 drugs of 2012,” July 2013). It has received attention in the media recently for its possible implication in the suicide of American rock/grunge musician Chris Cornell (CNN “Chris Cornell Used Prescription Before Death, Toxicology Report Says,” June 2017).

 
Ativan is a benzodiazepine, which are CNS (central nervous system) depressants that aid in slowing and calming down the central nervous system and thus reducing anxiety. (PubMed Health “Lorazepam” May 2017).

 
Ativan is also commonly used for insomnia and alcohol withdrawal. In addition, Ativan is used to treat continuous seizures, agitation, irritability, mania, and schizophrenia, and used as medication before anesthesia. (Stanford Medicine “Lorazepam,” 2017).

 
Ativan is only intended for short-term use. According to Stanford Medicine, if misused, it can cause serious side effects such as acidosis (excess amount of acid in the body), drug dependence, and unusual and dangerous behavior. Moreover Ativan, like other benzodiazepines, is highly addictive causing physical and psychological dependence.

 

How Ativan is Associated with Suicidal Behaviors

 
Medical experts report that benzodiazepine could cause anterograde amnesia. Those with anterograde amnesia can exhibit dangerous behaviors, such as intoxicated driving, committing crimes, and attempting suicide. (PubMed “Anterograde Amnesia Linked to Benzodiazepines” October 1992).

 
A toxicology report recently released showed that seven drugs, including a significant dose of Ativan, were found in Cornell’s system. However, the medical examiner said drugs did not contribute to Cornell’s death, but that instead Cornell committed suicide. (CNN “Chris Cornell Used Prescription Before Death, Toxicology Report Says,” June 2017).

 
According to experts, long-term use of Ativan can cause depression and negative mood in those with a history of depression and suicidal ideation. However, they advised that if someone was to die of an Ativan overdose or blackout, underlying mental health issues could have also played a role. (American Addiction Centers “The Dangers of Long-Term Use of Ativan” 2017).

 

Research Confirms Benzodiazepines Use Connected with Self-Harm

 
Research has shown an association between self- harm and suicide and benzodiazepine usage (The British Journal of General Practice “Self-harm and Suicide Associated with Benzodiaepine Usage” May 2007).

 
The case report found that a patient self-inflicted stab wounds twice in a month after his benzodiazepine dosage was changed. The researchers also examined another study that showed a significant correlation between benzodiazepine and suicide in the elderly. The report concludes that although these effects are rare, prescribers should be aware of how a strong dependence on benzodiazepine is developed quickly.

 

Know Your Risks with the Rxight® Genetic Test

If you are taking or plan to take Ativan (lorazepam) and are concerned about side effects such as these, consider the Rxight® genetic test to analyze your genetic risks. Rxight® is a pharmacogenetic program made just for you. Your doctor and pharmacist work together to create an accurate, reliable, and easy to understand treatment plan to minimize harmful drug effects and get you on the right medications.

 
Contact us for more information about how Rxight® can benefit you through phone at 1-(888) 888-1932 or email at support@Rxight.com.

Antipsychotic Medications in Schizophrenia

By | Antipsychotics, Pharmacogenetic Testing, Pharmacogenomics, Precision Medicine, Psychiatric Medications | No Comments

Medications are central to the treatment of schizophrenia and a number of drugs are used to treat this serious mental condition. Schizophrenia is a long-term mental disorder marked by psychosis- a breakdown in the relation between thought, emotion, and behavior, leading to errors in perception, inappropriate actions and feelings, withdrawal from reality, and a sense of mental fragmentation.

 

Most patients are now treated with antipsychotics that are thought to control symptoms through the brain chemical, dopamine. There are two types of antipsychotics used: first generation and second generation.

 

First Generation Antipsychotics

 
The first generation antipsychotics have more serious side effects and are used only when necessary. They include haloperidol (Haldol), chlorpromazine (Thorazine), and Fluphenazine (Prolixin). Side effects of first-generation antipsychotics include extrapyramidal side effects which is marked by rigidity, bradykinesia, dystonias, tremor, and akathisia. Tardive dyskinesia (TD)— a disorder marked by permanent involuntary movements in the limbs and face such as grimacing and lip-smacking – is another adverse effect that can occur with first-generation antipsychotics. Additionally. first-generation antipsychotics are known to cause cardiac rhythm abnormalities.

 

Second Generation Antipsychotics and Side Effects

 
The newer second generation antipsychotics have less side effects than the older drugs, and are preferred for treatment of schizophrenia. They include: aripiprazole (Abilify), asenapine (Saphris), brexipiprazole (Rexulti), clozapine (Clozaril), Iloperidone (Fanapt), Lurasidone (Latuda), Olanzapine (Zyprexa), Paliperidone (Invega), quetiapine (Seroquel), risperidone (Risperdal), and ziprasidone (Geodon).

 
Abilify side effects include akathisia (agitation), restlessness, insomnia, constipation, fatigue and blurred vision. Most of the second-generation antipsychotics have similar side effects, as they are similar chemically. Geodon is one of the newer antipsychotics with extra-pyramidal side effects reported (drug induced movement disorders).

 
During initial phases of treatment with the second generation antipsychotics patients may experience side effects such as dry mouth, drowsiness, restlessness, muscle spasms, tremor or blurring of vision. The second generation antipsychotics have a much lower risk of tardive dyskinesia, a serious side effect of the older antipsychotics. It is possible to lessen side effects by either lowering the dose or by changing medications.

 

Antipsychotic Pharmacogenetics

 
Patients and physicians often work together to find a dose that results in the fewest side effects. Patients will often change medications if the side effects are severe and side effects lessen over time. One way to potentially avoid side effects for new medications and for newly prescribed schizophrenia medications is to have your drug metabolism genes tested. After the human genome was sequenced back in 2003, genome wide association studies showed that there is variation among the population in the genes that process medications. As a result, if there’s a drug-processing gene with variation, it may have trouble processing medications that are metabolized by that gene product.

 

Know Your Risks with the Rxight® DNA Test

 
The most state-of-the-art way to determine genetic variations is with the Rxight® pharmacogenetics test from MD Labs. This advance in pharmacogenetics means that a physician can determine beforehand what drugs may be safe to take and what drugs to avoid or require different doses than recommended. All that is required is a prescription from a physician and a cheek swab at a participating pharmacy.

 
You could benefit from this advance in precision medicine with the knowledge of your gene variations with your physician or other healthcare services. The Rxight® pharmacogenetics test determines your genetic susceptibilities for over 200 drugs on the market. You could also benefit from knowing how you might respond to drugs you may have to take in the future. Most importantly, you could get information that may change your current dosing and medication for fewer harmful side effects from your antipsychotic medication.

Uses, Side Effects and Pharmacogenetics of Antihypertensive Drugs

By | Adverse Drug Reactions, Antihypertensives | No Comments

An antihypertensive drug is any agent that reduces blood pressure. There are many different classes and are used in certain situations. They are prescribed for hypertension and help prevent events like transient ischemic attacks (TIAs), strokes, and myocardial infarction.
 
Classes of antihypertensive drugs include:

  • Diuretics
  • Calcium channel blockers
  • ACE inhibitors – used to treat hypertension but act by inhibiting angiotensin converting enzyme. This reduces activity of the renin angiotensin aldosterone system and reduces blood pressure. One example is ramipril.
  • Angiotensin II receptor antagonists
  • Adrenergic antagonists
  • Benzodiazepines
  • Renin inhibitors
  • Aldosterone receptor antagonists
  • Endothelin receptor blockers
  • Thiazide diuretics – used to treat hypertension and edema. They work by inhibiting the sodium chloride symporter. The increase in fluid loss decreases blood volume and reduced blood pressure. An example is bendroflumethiazide.


 

Antihypertensive Drugs Side Effects

 
Thiazide diuretics like bendroflumethiazide cause a number of side effects. These include:

  • Syncope (fainting)
  • Hypotension (low blood pressure)
  • Glaucoma
  • Gastric irritation
  • Nausea/vomiting
  • Diarrhea
  • Constipation
  • Abdominal pain
  • Rash

 
Calcium Channel Blockers include drugs like isradipine and verapamil. Side effects include:

  • Headache
  • Dizziness
  • Lethargy
  • Hypotension (low blood pressure)
  • Edema (swelling)
  • Pharyngitis (sore throat)
  • Fatigue
  • Malaise
  • Rash
  • Scalp irritation
  • Sleep disturbance
  • Myalgia (muscle pain)
  • Allergic reactions
  • Hypersensitivity
  •  
    ACE inhibitors are also associated with a number of side effects. These include:

    • Hypotension
    • Angina pectoris (chest pain)
    • Postural hypotension
    • Nausea/vomiting
    • Diarrhea
    • Abdominal discomfort
    • Dyspepsia
    • Fatigue
    • Asthenia
    • Vertigo
    • Bronchitis
    • Cough
    • Depression
    • Anxiety
    • Nervousness
    • Restlessness
    • Headache
    • Dizziness
    • Syncope (fainting)
    • Muscle spasm
    • Myalgia (muscle pain)


     
    Angiotensin II receptor antagonists include drugs like losartan (Cozaar). Common side effects include:

    • Nasal congestion
    • Sinusitis
    • Abdominal pain
    • Nausea
    • Diarrhea
    • Dyspepsia (indigestion)
    • Back pain
    • Myalgia (muscle pain)
    • Dizziness
    • Headache
    • Vertigo
    • Chest pain
    • Hyperkalemia (high blood concentration of potassium)
    • Insomnia
    • Anemia

     
    Adrenergic receptor antagonists are also used as antihypertensives. Common side effects include (these occur in more than 1% of patients):

    • Hypotension (low blood pressure)
    • Raynaud’s syndrome (can result in cold extremities)
    • Fatigue
    • Sleep disturbances
    • Nightmares
    • Sleep disorder
    • Agitation
    • Somnolence (lack of energy)
    • Irritability

     
    Antianxiety medications such as benzodiazepines can be used to lower blood pressure. Side effects can include:

    • Irritability (33% more)
    • Anxiety
    • Depression
    • Confusion
    • Disinhibition
    • Derealization
    • Dream abnormalities
    • Fear
    • Drowsiness (77%)
    • Impaired coordination
    • Memory impairment
    • Lightheadedness
    • Insomnia
    • Headache
    • Cognitive disorder
    • Dysarthria
    • Abnormal involuntary movement
    • Somnolence
    • Ataxia (loss of control of body)
    • Balance disorder
    • Nervousness
    • Syncope (fainting)
    • Agitation
    • Paresthesia (pins and needles)
    • Tinnitus
    • Hypersomnia
    • Lethargy
    • Fatigue
    • Blurred vision
    • Decreased libido
    • Micturition difficulties (issues urinating)
    • Menstrual disorders
    • Increased libido
    • Decreased salivation
    • Constipation
    • Allergies
    • Tachycardia (increased heart rate)
    • Chest pains
    • Rigidity
    • Tremor
    • Muscular twitching
    • Increased/decreased appetite
    • Weight gain/loss

     

    Know Your Risks for Side Effects from Anihypertensive Medications with the Rxight® Genetic Test

     
    Most patients do not suffer adverse reactions when taking antihypertensives. However some patients may suffer from many side effects. This inter patient variability is explained by pharmacogenetics. Polymorphisms (variations) in the enzymes and receptors that interact with antihypertensives can increase the probability of patients developing side effects.
     
    Most antihypertensives are metabolized by the cytochrome P450 superfamily of enzymes (the specific isoenzymes will vary on class and drug). Polymorphisms in these enzymes have been shown in studies to increase the probability of developing side effects (Clinical Biochemist Reviews, “The Influence of Cytochrome P450 Pharmacogenetics on Disposition of Common Antidepressant and Antipsychotic Medications,” Feb 2006).
     
    Identifying these alleles can aid clinicians in prescribing antihypertensives and could reduce the risk of developing adverse reactions. MD Labs provides a genetic testing service, Rxight®, which sequences a number of genes to establish how patients are likely to respond to hundreds of medications, including most antihypertensives.

    side effects of opioids

    Pharmacogenomic Data May Help Guide Opioid Pharmacotherapy in Patients with Cancer-related Pain

    By | Cancer Treatments, Other, Pain Medications, Pharmacogenomics, Provider | No Comments

    Opioids are the most potent analgesics and are used to treat severe pain, specifically pain associated with cancer – a significant factor in reducing quality of life and clinical outcomes in such patients as detailed in Cancer Control “Clinical Implications of Opioid Pharmacogenomics in Patients with Cancer” (October 2015).

     

    Inter-individual Differences in Genetically Modulated Opioid Response

     
    The study reviewed clinical studies involving the pharmacodynamics and pharmacokinetics of opioids. It examined the opioid agents morphine, codeine, tramadol, oxycodone, fentanyl, and hydrocodone and the relationship to single nucleotide polymorphisms (SNPs): OPRM1, COMT (specifically COMT Val Met), CYP2D6, CYP3A4/5, and ABCB1, which the study claimed are responsible for the inter-individual differences in opioid response.

     
    The authors specifically found that OPRM1, COMT Val Met, and ABCB1 are most strongly correlated with morphine response. One study combined OPRM1 and ABCB1 and found that patients with both of these genetic variants were the best responders as indicated in patients’ measures of pain intensity. In another study, patients with OPRM1 and COMT Val Met needed the lowest morphine dose compared to other genotypes. All three together demonstrated no difference in morphine dose requirements.

     

    CYP2D6 Variants Correlate with Drug Efficacy

     
    Similarly, the presence of CYP2D6 variants correlated positively with variations in codeine and tramadol efficacy. CYP2D6 is responsible in converting the analgesic properties of codeine and tramadol. In studies investigating codeine pharmacotherapy in cancer patients, analgesic differences and adverse effects were found for CYP2D6 poor, intermediate, and extensive metabolizers.

     
    The authors concluded CYP2D6 testing helps in finding which patients respond positively to codeine. Studies with tramadol focusing on non-cancer pain populations identified CYP2D6 poor metabolizers as having a decreased analgesic response compared to extensive metabolizers. However, the authors noted there has been no specific study relating to tramadol’s analgesic efficacy in cancer populations, arguing tramadol will likely have decreased clinical benefit in patients who are poor CYP2D6 metabolizers.

     

    Call for Preemptive Genotyping in Clinical Practice

     
    The authors assert that these findings “suggest genotyping patients for some of these genetic variants may help predict responses to pain treatments with good rates of sensitivity and specificity and with greater benefits for patients and decreased health care utilization.” Furthermore, the authors assert that utilizing pharmacogenomics data combined with a preemptive genotyping be a “key element” in guiding treatment decisions for cancer patients.

    Overview of the Dangers and Side Effects of Psychotropic Medications

    By | ADHD Medications, Antianxiety Medications, Antidepressants, Antipsychotics, Pharmacogenetic Testing, Precision Medicine, Psychiatric Medications | No Comments

    Get the Rxight® Genetic Test to Know Your Risks

    Psychiatric medications (often called “psychotropics”) are routinely used to treat a variety of psychiatric disorders – ranging from ADHD (attention deficit hyperactive disorder) and depression to bipolar disorder and anxiety to schizophrenia – Psychiatric medications are generally jused as an adjunct to psychotherapy.

     
    It is estimated that 17 percent (some 80 million people) in the United States are taking some form of psychiatric medication (Scientific American, “1 in 6 Americans Takes a Psychiatric Drug,”  Dec 13 2016) According to the article, an earlier government report, from 2011, found that just over 10% of adults are taking prescription drugs for “problems with emotions, nerves or mental health,” published in the journal JAMA Internal Medicine.

     
    While the potential benefits of psychotropic medications have been demonstrated in research and clinical practice for decades, patients are cautioned to remain vigilant of the many side effects of psychiatric medications.

     
    This article presents a detailed summary of the major types of mental health medications and their associated risks for side effects as reported by the U.S. Food and Drug Administration (FDA) and the National Institute of Mental Health (NIMH) and an overview of the benefits of the Rxight® genetic test for psychiatric medications in identifying your unique genetically determined risk for developing side effects or non-response to dozens of these psychiatric medications along with hundreds of other medications across 50 pharmacological classes.

    Antidepressant Side Effects

    What are antidepressants?
    Antidepressants are commonly used to treat depressive disorders. They also are used for other conditions, such as pain, anxiety and insomnia. Although antidepressants are not FDA-approved specifically to treat ADHD, they are sometimes used “off-label” for ADHD treatment.

    The most commonly prescribed types of antidepressants today are called . Examples of SSRIs include:

    Other types of antidepressants are serotonin and norepinephrine reuptake inhibitors (SNRIs) .These are chemically similar to SSRIs and include and duloxetine (Cymbalta)  and venlafaxine (Effexor).

     
    Another antidepressant that is commonly used is bupropion – a third sub-class of antidepressant which acts differently than either SSRIs or SNRIs.  Bupropion is also used to treat seasonal affective disorder (SAD) and for smoking cessation treatment.

    SSRIs, SNRIs, and bupropion are commonly used today because they do not cause as many side effects as the older (“first generation”) classes of antidepressants, and moreover are effective in treating a broader range of depressive and anxiety disorders.

     
    Older antidepressant medications include tricyclic antidepressants, tetracyclic antidepressants, and monoamine oxidase inhibitors (MAOIs).  These are less commonly prescribed since the development of the newer generation antidepressants.
     
    What are the possible side effects of antidepressants?
    Some antidepressants may cause more side effects than others. The most common side effects listed by the FDA include:

    • Sexual problems (impotence or inability to orgasm)
    • Nausea and vomiting
    • Weight gain
    • Sleepiness or fatigue
    • Diarrhea

    In 2004, the FDA ordered a “black box” label – the most serious warning it issues – on all antidepressants to caution of psychiatric drugs’ increasing suicide risk in children and adolescents. In 2006, the FDA increased the age to include young adults up to age of 25. (FDA, Revision to Product Labeling, 2004)

     
    Call your doctor immediately if you have any of the following symptoms, especially if they are new, worsening, or worry you (U.S. Food and Drug Administration, 2011):

    • Suicidal thoughts or actions
    • New or worsening depression
    • New or worsening anxiety
    • Feeling restless or agitated or
    • Panic attacks
    • Insomnia
    • New or worsening irritability
    • Acting aggressively, being angry, or violent
    • Acting on dangerous impulses
    • An increase in activity and talking (mania)

    Additionally, drug interactions can occur.  Specifically, combining the newer SSRI or SNRI antidepressants with one of the commonly-used “triptan” medications for treating migraines can cause a life-threatening condition called “serotonin syndrome.” Serotonin syndrome is marked by agitation, hallucinations, high temperature, or unusual blood pressure changes. Serotonin syndrome is usually associated with the older antidepressants called MAOIs, but it can happen with the newer antidepressants as well.

     
    Antidepressants may cause other side effects that were not included in this list, as determined by individual genetics and ability to metabolize the drug in the liver.

     
    How do patients respond to antidepressants?
    Some people respond better to some antidepressant medications than to others.  It is critical to know that some people may not feel better with the first medicine they try. Additionally, sometimes people taking antidepressants feel better and stop taking the medication too soon, and the depression may return.

     
    These inter-individual differences are based in genetics, and the Rxight® genetic test will indicate which antidepressants may not work for you right from the start instead of having to go through trial and error with your doctor  With Rxight results, you your doctor can work together to find the best and most effective antidepressant treatment tailored to your unique genetics.

     

    Antipsychotic Side Effects

    What are antipsychotics?
    Antipsychotic medicines are primarily used to manage psychosis, a condition that affects the mind. Psychosis is characterized by some loss of contact with reality, often including or hallucinations (hearing or seeing things that are not really there), or delusions (false, fixed beliefs). It can also be a symptom of a physical condition such as drug abuse or a mental disorder such as schizophrenia, very severe depression (also known as “psychotic depression”), or bipolar disorder.

     
    Antipsychotic medications are frequently used in combination with other drugs to treat delirium, dementia, and mental health conditions, including:

    The older antipsychotic medications are conventionally referred to as “typical” antipsychotics or “neuroleptics”. Some of the common typical antipsychotics include:

    Second generation antipsychotic medications are also called “atypical” antipsychotics. Some of the most common atypical antipsychotics are:

    According to a 2013 research review by the Agency for Healthcare Research and Quality , typical and atypical antipsychotics both work to treat of bipolar disorder (preventing mania) and symptoms of schizophrenia Additionally, some atypical antipsychotics have wider applications and are used for treating bipolar depression or general depression.

     
    What are the possible side effects of antipsychotics?

    Antipsychotics are known to have a large number of side effects (also called adverse events) and risks, including potentially fatal complications.

     
    The FDA lists the following side effects of antipsychotic medicines:

    • Constipation
    • Nausea
    • Vomiting
    • Uncontrollable movements, such as tics and tremors (the risk is higher with typical antipsychotic medicines)
    • Seizures Drowsiness
    • Blurred vision
    • Low blood pressure
    • Dizziness
    • Restlessness
    • Weight gain (the risk is higher with some atypical antipsychotic medicines)
    • Dry mouth
    • A low number of white blood cells, which fight infections

    Typical antipsychotic medications can also cause additional side effects related to physical movement, such as:

    • Tremors
    • Restlessness
    • Rigidity
    • Muscle spasms

    Long-term use of antipsychotic medications may lead to a condition called tardive dyskinesia (TD). Tardive dyskinesia causes uncontrolled muscle movements, commonly around the mouth. TD can range from mild to very severe, and in some people, the problem cannot be cured and becomes disfiguring.

     
    Avoid the Risk of Antipsychotic Side Effects with Rxight®

    The Rxight® medication panel includes 18 popular antipsychotics on the market. Because the potential side effects of both typical and atypical antipsychotics can be very serious and potentially fatal, knowing your risks ahead of time with Rxight® can be an invaluable test for you and your prescriber.

     

    Mood Stabilizer Side Effects

    What are mood stabilizers?
    Mood stabilizers work by decreasing abnormal brain activity. They are used mainly to treat bipolar disorder and the mood swings associated with other mental conditions including:

    • Depression (usually in conjunction with an antidepressant)
    • Disorders of impulse control
    • Schizoaffective Disorder

    Anticonvulsant (anti-seizure) medications are most frequently used as mood stabilizers. They were originally developed for treatment of seizures, but they were found to help control mood swings as well. One anticonvulsant commonly used as a mood stabilizer especially in patients with symptoms of both mania and depression, or those with rapid-cycling bipolar disorder, is valproic acid (sold as Depakote). Anticonvulsants used as mood stabilizers include:

    Lithium is a non-anticonvulsant mood stabilizer approved for the treatment of mania and the maintenance treatment of bipolar disorder.

     
    What are the potential side effects of mood stabilizers?

    Mood stabilizers can cause several side effects, some of which may be serious, especially at high dosages. These side effects include:

    • Potentially fatal rash (Stevens-Johnson Syndrome)
    • Itching
    • Extreme thirst
    • Tremor
    • Nausea and vomiting
    • Fast, slow, or irregular heartbeat
    • Slurred speech
    • Blackouts
    • Changes in vision
    • Hallucinations
    • Loss of coordination
    • Swelling

    Mood stabilizers may cause other side effects that are not included in this list. Your unique reaction to anticonvulsants is based in genetics, and the Rxight® genetic test will indicate which mood stabilizer not work for you may right from the start instead of having to go through trial and error with your doctor – a process which can be expensive, lengthy and dangerous.  With Rxight® results, you your doctor can work together to find the best and most effective antidepressant treatment tailored to your genotype, preferably before treatment begins.

     

    Anti-Anxiety Medication Side Effects

    What are anti-anxiety medications?
    Anti-anxiety medications (also called “anxiolytics”) work by reducing the symptoms of anxiety, such as that seen in panic attacks, or extreme worry and fear. The most commonly prescribed anti-anxiety medications are called “benzodiazepines.” Benzodiazepines are most frequently used to treat a condition called generalized anxiety disorder, while in cases of social phobia (social anxiety disorder) or panic disorder (panic attacks). Benzodiazepines are usually second-line treatments, behind antidepressants such as SSRIS.

    Benzodiazepines used to treat anxiety disorders – all of which are tested in the Rxight® panel – include:

    Short-acting benzodiazepines such as Lorazepam and another class of medication known as beta-blockers are used to treat non-persistent symptoms of anxiety. Beta-blockers are used primarily to manage physical symptoms of anxiety (e.g., shaking, rapid heartrate, and sweating).

     
    Buspirone  (which is chemically unrelated to the benzodiazepine family) is sometimes indicated for the long-term treatment of chronic anxiety. It is not effective to use on an “as-needed” basis like the benzodiazepines.

     
    How common is addiction to benzodiazepines?
    One of the serious risks of anti-anxiety medications is that you can build up a tolerance to benzodiazepines if they are taken over a long period of time and may need increasingly higher doses to get the same effect. There is a serious risk of addiction and dependence. To avoid these problems, doctors usually prescribe benzodiazepines for short periods, particularly in the elderly (NIMH, “Despite Risks, Benzodiazepine Use Highest in Older People”), and people with addiction tendencies. If people suddenly stop taking benzodiazepines, they may have withdrawal symptoms or their anxiety may return.

     
    What are the possible side effects of anti-anxiety medications?
    Like other medications, anti-anxiety medications may cause side effects, many of which are serious. The most common side effects of benzodiazepines are sleepiness and dizziness. Other possible side effects include:

    • Headache
    • Confusion
    • Tiredness
    • Nausea
    • Blurred vision
    • Nightmares

    Tell your doctor immediately if any of these symptoms are severe or do not go away:

    • Drowsiness
    • Difficulty thinking or remembering
    • Increased saliva
    • Dizziness
    • Unsteadiness
    • Problems with coordination
    • Blurred vision

    If you experience any of the symptoms below, call your doctor immediately:

    • Swelling of the eyes, face, lips, tongue, or throat
    • Difficulty breathing or swallowing
    • Rash
    • Hives
    • Hoarseness
    • Seizures
    • Yellowing of the skin or eyes (jaundice)
    • Depression
    • Difficulty speaking
    • Difficulty breathing

    Common side effects of beta-blockers include:

    • Fatigue
    • Dizziness
    • Weakness
    • Cold hands

     

    Stimulant Side Effects

    What are Stimulants?
    Stimulants increase alertness, attention, and energy, as well as elevate blood pressure, heart rate, and respiration. Stimulant medications are generally prescribed to treat individuals diagnosed with ADHD (attention-deficit hyperactivity disorder). People with ADHD who take prescription stimulants describe a calming and “focusing” effect from the medication.  This is due to its effects on the brain chemical dopamine.

    Stimulants used to treat ADHD – all of which are analyzed in the Rxight® DNA test – include:

    In 2002, the FDA approved non-stimulant medication atomoxetine (Strattera) for use as a treatment for ADHD. Additional non-stimulant antihypertensive medications, clonidine  and guanfacine, are also approved for treatment of ADHD.

    In addition to treating ADHD, stimulants are prescribed to treat other health conditions, including narcolepsy, and occasionally depression.

     
    What are the possible side effects of stimulants?
    Stimulants may cause side effects, most of which are relatively minor and disappear when dosage levels are lowered. The most common side effects include:

    • Loss of appetite
    • Insomnia
    • Stomach pain
    • Headache

    Less common side effects include:

    • Motor tics or verbal tics
    • Personality changes

    What are serious side effects of stimulant medications?
    While side effects of stimulant medications tend to be minimal, patients and parents of patients are cautioned that serious adverse effects may occur, as reported by the FDA Drug Safety Communication in 2013. Also see
    FDA Warns of Psychiatric Adverse Events from ADHD Medications
    .

     
    Heart-related problems:

    • Sudden death in patients who have heart problems or heart defects
    • Stroke
    • Myocardial infarction (heart attack)
    • Increased blood pressure and heart rate

    Mental (Psychiatric) problems:

    • Behavior and thought problems
    • New or worse aggressive behavior or hostility
    • New or worse bipolar illness
    • New psychotic symptoms (or new manic symptoms)
    • Physical or psychological dependence

    For additional details on the FDA warnings and manufacturer labeling for medications covered in the Rxight® panel, please refer to our list of medications covered.

     

    About Rxight® Pharmacogenetic Testing

    The Rxight® genetic test analyzes your risks based on your unique genetic makeup through a process called “SNP genotyping.” The report which will be shared with you in a personal consultation with a pharmacist. The report “red-flags” medications which may cause you to have issues, or conversely highlight medications which may not be effective for you.

     
    Rxight® is based on pharmacogenetics — the study of how genes affect a person’s response to medicines. Our panel of over 200 clinically significant medications includes dozens of commonly prescribed psychiatric medications, including antidepressants across five sub-classes, mood stabilizers used in bipolar disorder and schizoaffective disorder, antipsychotics, ADHD medications (stimulant and non-stimulant), and anti-anxiety medications.

     
    Based on how well you metabolize those particular medications, which is determined by your genes that encode liver enzymes that break down drugs, you will be at risk for developing side effects or the medication not working well or at all. With the results of the Rxight® test you and your prescriber can find the right medication for you, preferably before treatment begins.

     
    Contact us today by phone 1 (888) 888-1932 or email to learn more about how Rxight® pharmacogenetic testing can help you find the right medication, right from the start.

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