Medical Genetics - V. M. Zaporozhan 2005

Multifactorial Diseases
Pharmacogenetics
Changes in Drug Responses in Patients with Hereditary Diseases

Some Hereditary diseases are accompanied by an altered physiological response to drug administration (Table 7.13). For instance, hepatic Porphyrias are determined by autosomal dominant genes that cause an increase in The activity of the mitochondrial Liver enzyme delta-aminolevulinic acid synthetase. The intake of barbiturates leads to a sharp increase in the levels of this acid and porphobilinogen in The Liver and urine, which triggers a disease attack. The main symptoms include severe abdominal pain, polyneuritis, psychiatric disorders, and epileptiform manifestations. An attack can be provoked not only by barbiturates, but also by sulfonamides, estrogens, meprobamate, and griseofulvin. Prescribing barbiturates for therapy to such patients can be fatal.

In hereditary methemoglobinemias, the Blood concentration of methemoglobin in patients is elevated up to 30% (normal is 1%). The causes of methemoglobinemia are Hemoglobin anomalies (Autosomal dominant inheritance) or decreased activity of methemoglobin reductase (Autosomal Recessive Inheritance). In patients with methemoglobinemia, mild oxidizing agents (such as methylene blue, ascorbic acid, sulfonamides, nitroglycerin, PAS, quinine, etc.) induce The conversion of normal hemoglobin into methemoglobin. Patients develop pronounced cyanosis, and methemoglobinemia persists for up to 12 hours. One of the consequences of methemoglobinemia is a marked resistance to hydrogen cyanide and its salts. Affected individuals can ingest a dose of K cyanide that is 40 times the lethal dose without significant consequences.

Ecogenetics and pharmacogenetics represent one of the most promising fields in modern preventive medicine. Determining individual characteristics of xenobiotic METABOLISM will make it possible to recommend optimal Nutrition, select appropriate drug therapy, and serve as one of the criteria for occupational guidance.