Introduction:
This study focused on the drug Carbamazepine (CBZ), a very common antiepileptic agent, which is mainly used for tonic-clonic seizures, facial and tongue pain and even bipolar disorder. Despite the cost effectiveness of CBZ, it also brings forward a few areas of concern. CBZ has been shown to produce various clinical responses within patients and unpredictable adverse events such as fatal allergic reactions and liver failure. This downfall occurs in roughly 30-50% of the patients prescribed CBZ. Many patients also develop resistance to CBZ. CBZ concentrations in the patients’ plasma and CNS are associated with the efficacy and toxicity of the drug, which gives rise to the study at hand. This study discussed the screening of patients, before beginning CBZ therapy, for potential markers associated with CBZ efficacy and toxicity.
Carbamazepine is absorbed very slowly in the body and is metabolized mainly by the hepatic genes, CYP3A4 and CYP2C8, to form carbamazepine 10-11 epoxide (CBZ-E). CBZ-E is then metabolized further, by EPHX1, into an inactive form and excreted in urine. The plasma level of CBZ-E, in adults, is about 15-55% of the dose of CBZ given. Carbamazepine also undergoes autoinduction and induces its own metabolism shortly after administration of the drug, leading to decreased plasma levels [1]. Mutations in drug transporter genes, ABCB1 and ABCC2, have also been associated with drug resistant epilepsy and low plasma concentrations of CBZ. In addition, nuclear hormone receptor genes (like NR1I2) are also associated with the transcriptional activation of drug transporters and CYP genes. Due to the many genes associated with the pharmacokinetics (efficacy, bioavailability and toxicity) of CBZ, interpatient ...
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...d and excreted in urine. A mutation in ABCB1 also was linked to high CBZ CL in African-Americans only. The study also associated a variation in NR1I2, causing activation of CYPs and transporters, with CBZ CL and the CBZ-E: CBZ ratio, meaning higher plasma concentrations of CBZ. Although this study did show associations between variations in genetics and pharmacokinetics, future studies must be conducted with a larger sample size to validate the findings. These findings are significant because, in the future epilepsy will be able to be classified by its oligogenic architecture and pharmacogenetic characteristics, providing the appropriate therapy for patients. [3]. This study is extremely important not only for determining genes mutations’ effects for future patient therapy but also in setting the stage future studies to conduct research and have a comparison point.
There are also explanations dealing with clozapine's interaction with the serotonin 5HT2 receptors and the glutamate receptors. ... ... middle of paper ... ... hin a week levels will increase with treatment of colazopine.(Naheed & Green, 2000) Andreasen, N.C. (1994).
The Catechol-O-methyltransferase (COMT) gene is a specialised type of enzyme, which is involved in the degradative processes of catecholamines. This process is a necessity in the human body, as prolonged exposure to catecholamines is detrime...
This paper will outline the background of Zolpidem; going through the history of the drug. The drugs path of movement through the body or the pharmacokinetics will also be explained. The process of absorption, distribution, and inactivation will be covered in the pharmacokinetics. Pharmacodynamics of the drug will be covered; explaining the sites of action and the areas of the brain that are affected by the drug. The potential for tolerance and dependence to be developed will also be examined. The level of toxicity of Zolpidem along with the potential side effects. The drug’s effectiveness as a form of psychotherapy will also be analyzed.
γ-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the CNS. GABAA is a ligand gated ion channel composed of five subunits. Through positive allosteric modulation ethanol binds to the δ subunit of the receptor and enhances the inhibitory effect of GABA. Once ethanol has bound to the GABAA receptor, chloride ions enter the post-synaptic neuron. This cascade of ions hyperpolarises the neuron, thus increasing inhibitory effects and makes the neuron less excitable. Ethanol alters the enzyme kinetics enabling the ion...
Epilepsy is a neurological disorder that affects the brain causing people to have seizures. A seizure is a big disruption of electrical communication between neurons, leading to the temporary release of excessive energy in a synchronized form Epilepsy is very unpredictable. Having a seizure disorder doesn't mean that you can only have one type of seizure. People can have many different types of seizures; it can vary on the person. In some cases depending on the type of seizures someone may have they can grow out of them. (“Epilepsy Foundation." What Is Epilepsy? N.p., n.d. Web. 09 May 2014.)
Benzodiazepine or know as benzo on the street. Benzos effect the central nervous system by slowing down the ...
Adverse drug events or medication errors that result from polypharmacy can often be difficult to predict and prevent. According to an article posted in the American Journal of Health-System Pharmacy (2012), drug –drug interactions may lead to increased toxicity levels when taken together. An example is the interactio...
Genetics predispose an individual to having an increased chance of becoming codependent upon drugs or alcohol. Studies of twins and of families that are prone to addiction suggest that about 50% of the risk for drug addiction is genetically based (EBSCOhost). One well-characterized relationship between genes and alcoholism is the result of variation in the liver enzymes that metabolize alcohol (NIH). The result of the liver breaking down the alcohol faster is a higher tolerance. Individuals with a higher tolerance to alcohol, need to drink more than the average person in order to seek the same biological effect. When heavy drinkers suddenly stop or significantly reduce their alcohol consumption, the neurotransmitters prev...
As we discussed above that pharmacokinetic and pharmacodynamics can be seen as two sides of the same coin in order to gain better understanding of their efficacy and safety profiles.” Generally it is possible to make fairly robust predictions of the pharmacokinetic profile in man using in vitro systems and preclinical pharmacokinetic studies. A previously published survey on the causes of failure in drug development indicated that inappropriate pharmacokinetics were a major cause such as; factors as low bioavailability due to high extraction or poor absorption characteristics, short elimination half-life leading to short duration of action and excessive variability due to genetic or environmental factors. This observation has led to an increased emphasis on pharmacokinetic input to the drug discovery process throughout the pharmaceutical industry. However, it is important to realise that this may only permit the rejection of compounds to b...
It was a cold, rainy day. I could see most of the kids at the bus stop had winter coats and hats. The clouds were particularly low in the sky. After evading the numerous puddles in the road, I reached the bus stop and walked up to a group of friends. A girl in my class spotted me and asked, "Are you going to the dance tomorrow?"
Kalliolias, George D., Athanasios G. Papavassiliou, and Gerasimos P. Sykiotis. "Pharmacogenetic principles in the hippocratic writings." Journal of Clinical Pharmacology 45.11 (2005): 1218+. Academic OneFile. Web. 30 Apr. 2014
Epilepsy is a very common neurological disorder. Some reports estimate that five in one-thousand people suffer from this problem. Throughout history, people with epilepsy have been shunned or considered inferior. Even today, ignorance leads many people to treat the epileptic as "abnormal" or "retarded". Although the etiology of epilepsy is still not fully understood, it is quite treatable due to advances in modern medicine.
Epilepsy is a condition characterized by recurrent seizures which are unprovoked by any immediately identifiable cause (Hopkins & Shorvon, 1995). It is also known as a seizure disorder. A wide range of links and risk factors are associated with the condition, but most of the time the cause is unknown. Epilepsy is one of the most common neurological disorders, affecting approximately two and half million people in the US and about 50 million worldwide. Though seizures can occur at any age, epilepsy is most commonly seen in children and the elderly. Most respond well to treatment and can control their seizures, but for some it is a chronic illness. A clinical diagnosis is the first step to finding a potential cure for the disorder.
National Institutes of Health. Retrieved [18th April 2011] from http://www.ninds.nih.gov/disorders/picks/picks.htm.
Sturgess, Jessica E., et al. "Pharmacogenetics Of Alcohol, Nicotine And Drug Addiction Treatments." Addiction Biology 16.3 (2011): 357-376. Academic Search Complete. Web. 12 Feb. 2014.