Uta

Uses

Hyoscyamine is an anticholinergic indicated to treat functional gastrointestinal disorders, biliary and renal colic, and acute rhinitis.

As a drug that is not FDA approved, hyscyamine has no official indications. Intravenous hysocyamine has been used to reduce gastric motility, reduce pancreatic pain and secretions, to facilitate imaging of the gastrointestinal tract, treat anticholinesterase toxicity, treat certain cases of partial heart block, improve visualization of the kidneys, and for symptomatic relief of biliary and renal colic. Intravenous hyoscyamine is also used pre-operatively to reduce secretions of the mouth and respiratory tract to facilitate intubation. Oral hyoscyamine is used to treat functional intestinal disorders, for symptomatic relief of biliary and renal colic, and symptomatic relief of acute rhinitis.

Methenamine is a urinary tract antiseptic and antibacterial drug used for the prophylaxis and treatment of frequently recurring urinary tract infections requiring a long-term therapy.

For prophylactic or suppressive treatment of frequently recurring urinary tract infections when long-term therapy is considered necessary. This drug is not used to treat infection and should only be used after appropriate eradication of infection with antimicrobial agents.

Methylene blue is an oxidation-reduction agent used for the treatment of pediatric and adult patients with acquired methemoglobinemia.

Indicated for the treatment of pediatric and adult patients with acquired methemoglobinemia.

Other clinical applications of methylene blue include improvement of hypotension associated with various clinical states, an antiseptic in urinary tract infections, treatment of hypoxia and hyperdynamic circulation in cirrhosis of liver and severe hepatopulmonary syndrome, and treatment of ifofosamide induced neurotoxicity.

Uta is also used to associated treatment for these conditions: Biliary Colic, Colic, Cystitis, Diverticulitis, Heart Block, Irritable Bowel Syndrome (IBS), Neurogenic Bladder Dysfunction, Neurogenic Bowel Dysfunction, Pancreatitis, Parkinsonism, Peptic Ulcer, Poisoning caused by anticholinesterases, Pylorospasm, Renal Colic, Spastic bladder, Tracheo-bronchial secretion excess, Acute Enterocolitis, Acute Rhinitis, Gastric secretions, Mild Dysentery, Pharyngeal secretions, Salivary secretions, Spastic colitisUrinary Tract InfectionCystitis, Methaemoglobinaemia, Nephritis, Urethritis, Urinary tract inflammation, Diuresis

How Uta works

Hyoscyamine competitively and non-selectively antagonises muscarinic receptors in the smooth muscle, cardiac muscle, sino-atrial node, atrioventricular node, exocrine nodes, gastrointestinal tract, and respiratory tract. Antagonism of muscarinic M1, M4, and M5 receptors in the central nervous system lead to cognitive impairment; antagonism of M2 in the sinoatrial and atrioventricular nodes leads to bradycardia and lowers contractility; and antagonism of M3 in smooth muscle results in reduced peristalsis, bladder contraction, salivary secretions, gastric secretions, bronchial secretions, sweating, increased bronchodilation, mydriasis, and cycloplegia.

Methenamine does not have antibacterial properties in an alkaline environment (pH≥6); however, in a more acidic environment (pH<6), methenamine is hydrolyzed to formaldehyde. (1) Formaldehyde is considered to be highly bactericidal. (1) Formaldehyde has nonspecific antibacterial activity and works by denaturing proteins and nucleic acid of bacteria. (1) Certain bacteria such as Proteus sp. can alkalize urine, inhibiting the beneficial activity of formaldehyde. (1) The key role of the salt component of the drug, for example hippuric acid, is to maintain the acidic state of the urine. (1)

• Main mechanism of action involves inhibition of nitric oxide synthase and guanylate cyclase.
• In Alzheimers Disease: a mechanistic study found that methylene blue oxidizes cysteine sulfhydryl groups on tau to keep tau monomeric. One preclinical treatment study in tauopathy mice reported anti-inflammatory or neuroprotective effects mediated by the Nrf2/antioxidant response element (ARE); another reported insoluble tau reduction and a learning and memory benefit when given early.
• In Methemoglobinemia: Methylene Blue acts by reacting within RBC to form leukomethylene blue, which is a reducing agent of oxidized hemoglobin converting the ferric ion (fe+++) back to its oxygen-carrying ferrous state(fe++).
• As antimalarial agent: Methylene Blue, a specific inhibitor of P.falciparum glutathione reductase has the potential to reverse CQ resistance and it prevents the polymerization of haem into haemozoin similar to 4-amino-quinoline antimalarials.
• For ifosfamide induced neurotoxicity: Methylene blue functions as an alternate electron acceptor. It acts to reverse the NADH inhibition caused by gluconeogenesis in the liver while blocking the transformation of chloroethylamine into chloroacetaldehyde. In addition, it inhibits various amine oxidase activities, which also prevents the formation of chloroacetaldehyde.

Toxicity

Patients experiencing an overdose may present with headache, nausea, vomiting, dizziness, dry mouth, difficulty in swallowing, dilated pupils, blurred vision, urinary retention, hot dry and flushed skin, tachycardia, hypertension, hypotension, respiratory depression, CNS stimulation, fever, ataxia, excitation, lethargy, stupor, coma, and paralysis. Patients should be treated with symptomatic and supportive therapy which may include emesis, gastric lavage, activated charcoal, artificial respiration, or intravenous physostigmine. Dialysis is expected to remove hyoscyamine sulfate from circulation.

Less than 3.5% of patients treated with this drug will experience minor adverse events such as upset stomach, dysuria, nausea, and rash.

LD50 = 1180 mg/kg ( Rat ).

Volume of Distribution

10 mg/kg (in rats).

Elimination Route

Hyoscyamine is completely absorbed by sublingual and oral routes, though exact data regarding the C_max, T_max, and AUC are not readily available.

After oral administration, rapid absorption of methenamine occurs. (1)

Half Life

The half life of hyoscyamine is 3.5 hours.

Elimination half-life = 3-4 hours assuming normal renal function. (1)

5–6.5 hours (after IV dose).

Clearance

70-90% of a single oral dose of methenamine is excreted unchanged in the urine within 24 hours. (1)

3.0 ± 0.7 L/min.

Elimination Route

The majority of hyoscyamine is eliminated in the urine as the unmetabolized parent compound.

Methenamine is primarily eliminated via the kidneys. (1)

Excreted in urine and bile. About 75% of an oral dose excreted in urine, primarily as stabilized colorless leukomethylene blue.

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