Pharmacogenetics can be defined as the study of genetic response related to drug response. Pharmacogenetics is a combination of Pharmacogenomics: the study of entire genome related to drug response, Pharmacokinetics: drug metabolism and Pharmacodynamics: interaction between drugs and their molecular targets. This is crucial where genetics come to control medicines. In general people say, a certain medicine would not work for one person, while another person can get healed from that for the same disease. Medical Practitioners ask the patient before prescribing medicine about drugs that may cause adverse reactions in their body which may be an antibiotic or any other kind of drug. These adverse reactions caused by drugs in certain people are most of the time genetically inherited. Therefore it is important to take a look at family history, when taking medicine as some responses may be fatal.
During the study of drug metabolism, it’s important to pay attention on absorption of drugs from gut, distribution, drug cell interactions, breakdown of drugs in liver and excretion.
Isoniazid is a drug used for the treatment of tuberculosis. After this drug is absorbed from gut, the level of the drug in blood is initially high and reduces slowly in healthy people. Due to genetic errors, the inactivation of the drug can be slow or rapid in some people. In rapid inactivators, the level of drug decreases rapidly in the blood. In contrast, the level of the drug remains high for some time in slow inactivators. Slow inactivators of this drug are homogenous for autosomal recessive allele which encodes liver enzyme N-acetyl transferase. High levels of isoniazid in blood can be harmful as it causes some side effects such as liver damage. Slow inactivators have a greater risk for this.
Succinyl Choline is a drug that is used for relaxation of muscles that was introduced in 1950’s. It is used in the induction phase of anesthesia which is metabolized by plasma enzyme cholinesterase. In sensitive patients, destruction is slower and resulted in respiratory arrest with the intake of the drug. Succinyl choline sensitivity is inherited as an autosomal recessive trait which is caused by mutations of CHE 1 gene. Sensitive patients can now be identified by a blood test that monitors cholinesterase activity.
Primaquinone is a drug used in treatment for Malaria. Some people were found to be sensitive to this drug. The sensitive people can take the drug for few days without any side effects, but starts to pass very dark/black urine. Jaundice, reduction in red blood cell count and Hemoglobin are symptoms produced by these sensitive people in response to the drug. This occurs due to a deficiency of the enzyme, Glucose 6-phosphate dehydrogenase which is a X linked recessive trait found commonly among Mediterraneans. Patients with the deficiency of this enzyme are also sensitive to drugs such as Phenacetin, Nitrofurantan, Sulfonamides. These drugs should be carefully used for treatments of these patients.
Coumarin(Warfarin) is an anticoagulant which is used in treatments for many diseases to prevent blood clotting. This drug is metabolized by cytochrome P450 encoded by the gene CYP2C9. Isoenzyme 2C9 is the functional enzyme in metabolizing the drug. VKORC1 is another gene important for degradation of this drug. This gene is involved in the production of target enzyme for warfarin action and it converts Vitamin K into an active form which activates Vitamin K dependent clotting factors.
Debrisoquine is used in the treatment of hypertension and it’s a derivative of guanidine. Many Europeans are poor metabolizers of this drug. This metabolic defects are due to an allele which is homozygous for autosomal recessive gene; CYP2D6 in P450 gene in chromosome 22. A mutation in this gene results in poor metabolism. This gene is involved in metabolism of many drugs.
Leukemia is also known as blood cancer. Thiopurines are used to suppress immune response in autoimmune conditions in patients with transplanted organs. This drug has serious side effects including severe liver damage. Poor metabolism of this drug is due to variations in thiopurine methyl transferase activity which is involved in methylation of thiopurines. This variability caused by genetic differences between people is one of the best examples for the importance of Pharmacogenetics in medicine.
During the study of drug metabolism, it’s important to pay attention on absorption of drugs from gut, distribution, drug cell interactions, breakdown of drugs in liver and excretion.
Isoniazid is a drug used for the treatment of tuberculosis. After this drug is absorbed from gut, the level of the drug in blood is initially high and reduces slowly in healthy people. Due to genetic errors, the inactivation of the drug can be slow or rapid in some people. In rapid inactivators, the level of drug decreases rapidly in the blood. In contrast, the level of the drug remains high for some time in slow inactivators. Slow inactivators of this drug are homogenous for autosomal recessive allele which encodes liver enzyme N-acetyl transferase. High levels of isoniazid in blood can be harmful as it causes some side effects such as liver damage. Slow inactivators have a greater risk for this.
Succinyl Choline is a drug that is used for relaxation of muscles that was introduced in 1950’s. It is used in the induction phase of anesthesia which is metabolized by plasma enzyme cholinesterase. In sensitive patients, destruction is slower and resulted in respiratory arrest with the intake of the drug. Succinyl choline sensitivity is inherited as an autosomal recessive trait which is caused by mutations of CHE 1 gene. Sensitive patients can now be identified by a blood test that monitors cholinesterase activity.
Primaquinone is a drug used in treatment for Malaria. Some people were found to be sensitive to this drug. The sensitive people can take the drug for few days without any side effects, but starts to pass very dark/black urine. Jaundice, reduction in red blood cell count and Hemoglobin are symptoms produced by these sensitive people in response to the drug. This occurs due to a deficiency of the enzyme, Glucose 6-phosphate dehydrogenase which is a X linked recessive trait found commonly among Mediterraneans. Patients with the deficiency of this enzyme are also sensitive to drugs such as Phenacetin, Nitrofurantan, Sulfonamides. These drugs should be carefully used for treatments of these patients.
Coumarin(Warfarin) is an anticoagulant which is used in treatments for many diseases to prevent blood clotting. This drug is metabolized by cytochrome P450 encoded by the gene CYP2C9. Isoenzyme 2C9 is the functional enzyme in metabolizing the drug. VKORC1 is another gene important for degradation of this drug. This gene is involved in the production of target enzyme for warfarin action and it converts Vitamin K into an active form which activates Vitamin K dependent clotting factors.
Debrisoquine is used in the treatment of hypertension and it’s a derivative of guanidine. Many Europeans are poor metabolizers of this drug. This metabolic defects are due to an allele which is homozygous for autosomal recessive gene; CYP2D6 in P450 gene in chromosome 22. A mutation in this gene results in poor metabolism. This gene is involved in metabolism of many drugs.
Leukemia is also known as blood cancer. Thiopurines are used to suppress immune response in autoimmune conditions in patients with transplanted organs. This drug has serious side effects including severe liver damage. Poor metabolism of this drug is due to variations in thiopurine methyl transferase activity which is involved in methylation of thiopurines. This variability caused by genetic differences between people is one of the best examples for the importance of Pharmacogenetics in medicine.
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