Prosed EC

Uses

Atropine is used for Non ulcer dyspepsia, Irritable bowel syndrome, Diverticular disease, Bradycardia, Organophosphorus poisoning, Premedication in anesthesia, Poisoning or overdosage with compound having muscarinic actions, Ophthalmic Inflammatory eye disorders, Eye refraction.

Benzoic acid is an antimicrobial food additive.

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.

Pain and fever .

Prosed EC is also used to associated treatment for these conditions: Amblyopia, Atrioventricular Heart Block, Bradycardia, Bronchospasm, Crying, Detrusor Hyperreflexia, Excessive bronchial secretion, Hypertonic uterine contraction, Hypertonicity of the small intestine, Ocular Inflammation, Parkinsonism, Peptic Ulcer, Poisoning by parasympathomimetics (cholinergics), Poisoning caused by mushrooms, Poisoning caused by organophosphate anticholinesterase nerve agents, Poisoning caused by organophosphorus pesticides, Pylorospasm, Rhinorrhoea, Sinus Bradycardia, Spasms, Toxic effect of organophosphate and carbamate, Hypermobility of the colon, Laughing, Muscarinic side effectsInfections, Fungal, Oropharyngeal pain, Pain, Ringworm, Sore Throat, Tinea Pedis, Burning sensation in the mouth, Dry cough, Mouth infection, Throat infectionsBiliary 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 Prosed EC works

Atropine binds to and inhibit muscarinic acetylcholine receptors, producing a wide range of anticholinergic effects.

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.

Inhibits the activity of the enzyme known as cyclooxygenase (COX) which causes the formation of prostaglandins, substances which cause inflammation, swelling, pain, and fever . For more information, refer to the drug entry Aspirin.

Dosage

Prosed EC dosage

Adult:

• IV: Bradycardia: 500 mcg every 3-5 mins. Total: 3 mg.
• IV/IM: Organophosphorus poisoning: 2 mg every 10-30 mins until muscarinic effects disappear or atropine toxicity appears.
• IM/SC: Premedication in anesthesia: 300-600 mcg 30-60 mins before anesthesia.
• IV/IM/SC: Poisoning or overdosage with compound having muscarinic actions: 0.6-1 mg, repeat 2 hrly.
• Ophthalmic: Inflammatory eye disorders: As 0.5-1% solution: 1-2 drops 4 times/day.
• Ophthalmic: refraction: 1% solution 1 drop twice daily for 1-2 days before procedure.
• Oral: Non ulcer dyspepsia, Irritable bowel syndrome, Diverticular disease: 0.6-1.2 mg as a single dose at bedtime.

Usual Pediatric Dose for Anesthesia:

• 7 to 16 pounds: 0.1 mg, IV, IM, or subcutaneously
• 17 to 24 pounds: 0.15 mg, IV, IM, or subcutaneously
• 24 to 40 pounds: 0.2 mg, IV, IM, or subcutaneously
• 40 to 65 pounds: 0.3 mg, IV, IM, or subcutaneously
• 65 to 90 pounds: 0.4 mg, IV, IM, or subcutaneously
• Over 90 pounds: 0.4 to 0.6 mg, IV, IM, or subcutaneously

Side Effects

Injection: Dry mouth, dysphagia, constipation, flushing and dryness of skin, tachycardia, palpitations, arrhythmias, mydriasis, photophobia, cycloplegia, raised intraocular pressure. Toxic doses cause tachycardia, hyperpyrexia, restlessness, confusion, excitement, hallucinations, delirium and may progress to circulatory failure and resp depression.

Eye drops or ointment: Systemic toxicity esp in children, on prolonged use may lead to irritation, hyperaemia, oedema and conjunctivitis. Increased intraocular pressure.

Toxicity

Oral, mouse: LD₅₀ = 75 mg/kg. Symptoms of overdose includes widespread paralysis of parasympathetically innervated organs. Dry mucous membranes, widely dilated and nonresponsive pupils, tachycardia, fever and cutaneous flush are especially prominent, as are mental and neurological symptoms. In instances of severe intoxication, respiratory depression, coma, circulatory collapse and death may occur.

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 ).

Oral LD50 in the rat is 3000 mg/kg

Adverse effects can be divided into several categories , :

Eyes: irritation

Skin: skin irritation

Cardiovascular: rapid pulse, flushing

Central Nervous System —blurred vision, dizziness

Respiratory —shortness of breath or troubled breathing , irritation of respiratory system

Genitourinary —difficult micturition, acute urinary retention

Gastrointestinal —dry mouth, nausea/vomiting

Overdosage may be managed by inducing emesis or gastric lavage. Slow intravenous administration of physostigmine in doses of 1 to 4 mg (0.5 to 1 mg in children) repeated as needed in 1-2 h to relieve severe antimuscarinic symptoms. Administration of small doses of diazepam to control excitement and seizures may be warranted. Artificial respiration with oxygen can be used if needed for respiratory depression. Adequate hydration is important, as well as symptomatic treatment, provided as necessary .

Precaution

Reflux oesophagitis; elderly; infants and children; Pregnancy.

Interaction

Additive anticholinergic effects with quinidine, antidepressants and some antihistamines.

Volume of Distribution

10 mg/kg (in rats).

Steady-state plasma salicylate concentrations increase more than proportionally with increasing dosages; the time required to reach steady state increases with increasing daily dose. Dosage intervals of 8-12 h are sufficient to maintain plasma salicylate concentrations in the normal therapeutic anti-inflammatory concentration range .

Elimination Route

Atropine is rapidly and well absorbed after intramuscular administration. Atropine disappears rapidly from the blood and is distributed throughout the various body tissues and fluids.

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)

Rapidly absorbed. Refer to Aspirin for detailed salicylate absorption information.

Half Life

3.0 ± 0.9 hours in adults. The half-life of atropine is slightly shorter (approximately 20 minutes) in females than males.

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).

Mean half-life of 1.1 h .

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.

Please refer to Aspirin for more information.

Elimination Route

Much of the drug is destroyed by enzymatic hydrolysis, particularly in the liver; from 13 to 50% is excreted unchanged in the urine.

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.

Please refer to Aspirin for the route of elimination.

Pregnancy & Breastfeeding use

Pregnancy Category C. Animal reproduction studies have not been conducted with atropine. It also is not known whether atropine can cause fetal harm when given to a pregnant woman or can affect reproduction capacity. Atropine should be given to a pregnant woman only if clearly needed.

Contraindication

Glaucoma, chronic respiratory disease, sick sinus syndrome, thyrotoxicosis, cardiac failure, pyloric stenosis, prostatic hypertrophy.

Acute Overdose

May cause hyperthermia, hypertension, increased respiratory rate, nausea and vomiting. May also lead to CNS stimulation. Severe intoxication may lead to CNS depression, coma, respiratory failure and death.

Storage Condition

Store atropine at room temperature between 20 to 25° C. Store away from heat, moisture, and light. Keep atropine out of the reach of children.

Innovators Monograph

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