Browsing Pathways

Levocetirizine is a second-generation piperazine H1-antihistamine. It has also been labeled as a third-generation antihistamine because it is developed from a second-generation antihistamine (cetirizine). H1-antihistamines interfere with the agonist action of histamine at the H1 receptor and are administered to attenuate inflammatory process in order to treat conditions such as allergic rhinitis, allergic conjunctivitis, and urticaria. Reducing the activity of the NF-κB immune response transcription factor through the phospholipase C and the phosphatidylinositol (PIP2) signalling pathways also decreases antigen presentation and the expression of pro-inflammatory cytokines, cell adhesion molecules, and chemotactic factors. Furthermore, lowering calcium ion concentration leads to increased mast cell stability which reduces further histamine release. First-generation antihistamines readily cross the blood-brain barrier and cause sedation and other adverse central nervous system (CNS) effects (e.g. nervousness and insomnia). Second-generation antihistamines are more selective for H1-receptors of the peripheral nervous system (PNS) and do not cross the blood-brain barrier. Consequently, these newer drugs elicit fewer adverse drug reactions.

Mepyramine (pyrilamine) is a first-generation ethylenediamine H1-antihistamine. H1-antihistamines interfere with the agonist action of histamine at the H1 receptor and are administered to attenuate inflammatory process in order to treat conditions such as allergic rhinitis, allergic conjunctivitis, and urticaria. Reducing the activity of the NF-κB immune response transcription factor through the phospholipase C and the phosphatidylinositol (PIP2) signalling pathways also decreases antigen presentation and the expression of pro-inflammatory cytokines, cell adhesion molecules, and chemotactic factors. Furthermore, lowering calcium ion concentration leads to increased mast cell stability which reduces further histamine release. First-generation antihistamines readily cross the blood-brain barrier and cause sedation and other adverse central nervous system (CNS) effects (e.g. nervousness and insomnia). Second-generation antihistamines are more selective for H1-receptors of the peripheral nervous system (PNS) and do not cross the blood-brain barrier. Consequently, these newer drugs elicit fewer adverse drug reactions.

Histapyrrodine is a first-generation ethylenediamine H1-antihistamine. H1-antihistamines interfere with the agonist action of histamine at the H1 receptor and are administered to attenuate inflammatory process in order to treat conditions such as allergic rhinitis, allergic conjunctivitis, and urticaria. Reducing the activity of the NF-κB immune response transcription factor through the phospholipase C and the phosphatidylinositol (PIP2) signalling pathways also decreases antigen presentation and the expression of pro-inflammatory cytokines, cell adhesion molecules, and chemotactic factors. Furthermore, lowering calcium ion concentration leads to increased mast cell stability which reduces further histamine release. First-generation antihistamines readily cross the blood-brain barrier and cause sedation and other adverse central nervous system (CNS) effects (e.g. nervousness and insomnia). Second-generation antihistamines are more selective for H1-receptors of the peripheral nervous system (PNS) and do not cross the blood-brain barrier. Consequently, these newer drugs elicit fewer adverse drug reactions.

Chloropyramine is a first-generation ethylenediamine H1-antihistamine. H1-antihistamines interfere with the agonist action of histamine at the H1 receptor and are administered to attenuate inflammatory process in order to treat conditions such as allergic rhinitis, allergic conjunctivitis, and urticaria. Reducing the activity of the NF-κB immune response transcription factor through the phospholipase C and the phosphatidylinositol (PIP2) signalling pathways also decreases antigen presentation and the expression of pro-inflammatory cytokines, cell adhesion molecules, and chemotactic factors. Furthermore, lowering calcium ion concentration leads to increased mast cell stability which reduces further histamine release. First-generation antihistamines readily cross the blood-brain barrier and cause sedation and other adverse central nervous system (CNS) effects (e.g. nervousness and insomnia). Second-generation antihistamines are more selective for H1-receptors of the peripheral nervous system (PNS) and do not cross the blood-brain barrier. Consequently, these newer drugs elicit fewer adverse drug reactions.

Isothipendyl is a first-generation phenothiazine H1-antihistamine. H1-antihistamines interfere with the agonist action of histamine at the H1 receptor and are administered to attenuate inflammatory process in order to treat conditions such as allergic rhinitis, allergic conjunctivitis, and urticaria. Reducing the activity of the NF-κB immune response transcription factor through the phospholipase C and the phosphatidylinositol (PIP2) signalling pathways also decreases antigen presentation and the expression of pro-inflammatory cytokines, cell adhesion molecules, and chemotactic factors. Furthermore, lowering calcium ion concentration leads to increased mast cell stability which reduces further histamine release. First-generation antihistamines readily cross the blood-brain barrier and cause sedation and other adverse central nervous system (CNS) effects (e.g. nervousness and insomnia). Second-generation antihistamines are more selective for H1-receptors of the peripheral nervous system (PNS) and do not cross the blood-brain barrier. Consequently, these newer drugs elicit fewer adverse drug reactions.

Ocular non-nephropathic cystinosis, also known as adult-onset cystinosis, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder of the cysteine metabolism pathway. It is caused by a defect in the CTNS gene, which encodes the protein cystinosin, which acts as a cystine/H+ symporter that transports L-cysteine out of the lysosome. Ocular non-nephropathic cystinosis is characterized by a buildup of cysteine in cells, in the case of this form in the cornea. Symptoms include photophobia and damage to the cornea due to crystals forming from the excess cysteine. However, unlike other forms of cystinosis, no or minimal kidney damage occurs. Treatment with cysteamine, a drug that can convert cysteine into a form that can be secreted by the lysosome, can be effective in all of the forms of cystinosis. It is estimated that ocular non-nephropathic cystinosis affects less than 1 in 100,000 to 200,000 individuals, which is the rate of the more severe nephropathic cystinosis.

Tyrosine Hydroxylase (TH) Deficiency is a rare inborn error of metabolism (IEM) and autosomal recessive disorder of catecholamines pathways. The disorder is caused by defects in the Tyrosine hydroxylase (TH) gene which encodes for the enzyme tyrosine hydroxylase. This enzyme is part of the production of catecholamines such as dopamine, norepinephrine and epinephrine are all essential for normal nervous system function. Dopamine transmits signals to help the brain control physical movement and emotional behavior. Norepinephrine and epinephrine are involved in the autonomic nervous system. Mutations in the TH gene result in reduced activity of the tyrosine hydroxylase enzyme. As a result, the body produces less dopamine, norepinephrine and epinephrine. Symptoms of the disorder include abnormal movements, autonomic dysfunction, and other neurological problems. Treatments can include the administration of levodopa; however patient responses can vary greatly. The frequency of Tyrosine Hydroxylase Deficiency is unknown.

Glycogen storage disease type VI, also called GSDVI or Hers disease, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder caused by a defective liver glycogen phosphorylase. Liver glycogen phosphorylase catalyzes the conversion of glycogen into amylose which is substrate of 1,4-alpha-glucan-branching enzyme and glycogen debranching enzyme. The disorder may show as enlarged liver in infancy to early childhood. Treatment may not required for some individuals. Glycogen storage disease type VI has been reported in approximately 11 people at least.

Hereditary fructose intolerance, also called hereditary fructose-1-phosphate aldolase deficiency or hereditary fructosemia, is rare inborn error of metabolism (IEM) and autosomal recessive disorder of the fructose and mannose degradation pathway. It is caused by a mutation in the ALDOB gene, which encodes fructose-bisphosphatse aldolase B, also known as aldolase B or liver-type aldolase. This enzyme normally cleaves fructose 1,6-bisphosphate into dihydroxyacetone phosphate and D-glyceraldehyde 3-phosphate, isomers of one another that are later used in glycolysis. Hereditary fructose intolerance is characterized by an accumulation of fructose-1-phosphate in the liver, as well as a depletion of ATP due to glycolysis having less input than necessary. Symptoms of this disorder include hypoglycemia, abdominal pain and vomiting as well as other symptoms after ingesting fructose. After repeated ingestion of fructose, liver and kidney damage can occur, as well as growth retardation, seizures, and even death. Hereditary fructose intolerance can be treated by eliminating fructose from the diet, and multivitamins can be prescribed to make up for the lack of fruits, a major source of fructose, in the diet. It is estimated that hereditary fructose intolerance affects 1 in between 20,000 and 30,000 individuals.

Glycogen storage disease type III, which is also known as GSD III or Cori disease, is a rare inherited inborn error of metabolism (IEM). GSD-III has an incidence of about 1 in 100 000. The incidence of GSD-III is higher in North African Jews (1 in 5 400), Faroese (1 in 3 100) and the Inuit population in Nunavik, Canada (1 in 2 500). GSDIII is an autosomal recessive metabolic disorder characterized a deficiency in glycogen debranching enzymes, specifically the enzyme amylo-1,6 glucosidase. GSD III causes a buildup of a complex sugar called glycogen in the body's cells. The accumulated glycogen is structurally abnormal and impairs the function of certain organs and tissues, especially the liver and muscles. GSD III typically presents during infancy with hypoglycemia and failure to thrive. Clinical examination usually reveals hepatomegaly. Muscular disease, including hypotonia and cardiomyopathy, usually occurs later in life. GSD III is divided into the types IIIa, IIIb, IIIc, and IIId, which are distinguished by their pattern of signs and symptoms. GSD types IIIa and IIIc affect primarily the liver and muscles. This is in direct contrast to GSD types IIIb and IIId which affect only the liver. Differentiating between the types of GSD III which affect the same tissue is extremely challenging. Out of all the GSD types, IIIa and IIIb are the condition's most common forms. Treatment for glycogen storage disease type III may involve a high-protein diet, in order to facilitate gluconeogenesis.